J Cancer 2017; 8(6):1103-1112. doi:10.7150/jca.17688
Tuberostemonine reverses multidrug resistance in chronic myelogenous leukemia cells K562/ADR
1. Tongren Hospital, School of Medicine, Shanghai JiaoTong University, 1111 Xianxia Road, Changning District, Shanghai 200336, China;
2. School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha 410013, China;
3. Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital, Central South University, 78 Xiangya Road, Changsha 410008, China;
4. School of Pharmacy, Yanbian University, 977 Park Road, Yanji 133000, China;
5. Hepatobilliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 78 Xiangya Road, Changsha 410008, China;
6. Shanghai First Maternity and Infant Hospital Corporation. 2699 Gaoke West Road, Pudong New Area, Shanghai, 201204, China.
* These authors contributed equally to this work
Objective: To investigate the reversal effect of tuberostemonine on MDR in myelogenous leukemia cells K562/ADR.
Methods: Human myelogenous leukemia cells K562 and their adriamycin-resistance cells K562/ADR were used. The growth curve of cells treated by tuberostemonine and the Non-toxic concentration of tuberostemonine were determined by MTT, Cell apoptosis was determined by MTT and flow cytometry. The expression of MDR1, Survivin and Livin was detected by RT-PCR. The activity of P-gp was detected by flow cytometry. Western blot was used to detect the expression of NF-κB and Survivin.
Results: The effect of tuberostemonine on K562/ADR showed a dose-dependence, and 350μg/mL and 500μg/mL of tuberostemonine could inhibit the expression of MDR1 (P<0.05). While no function difference of P-gp was detected. With the increased concentration of tuberostemonine, the inhibitory effect were enhanced to the expression of NF-κB. Tuberostemonine combined with adriamycin could time-dependently inhibit the cell proliferation (P<0.05) and obviously promoted the cell apoptosis (P<0.05). Also the tuberostemonine could inhibit the expression of Survivin.
Conclusion: There are no direct relations between tuberostemonine and P-gp, but tuberostemonine could reverse the multidrug resistance of K562/ADR via down-regulating the expression of Nf-κB and inhibiting th1e expression of Survivin.
Keywords: tuberostemonine, multidrug resistance, P-glycoprotein, K562/ADR, apoptosis.
Wang YJ, Zhao HD, Zhu CF, Li J, Xie HJ, Chen YX. Tuberostemonine reverses multidrug resistance in chronic myelogenous leukemia cells K562/ADR. J Cancer 2017; 8(6):1103-1112. doi:10.7150/jca.17688. Available from http://www.jcancer.org/v08p1103.htm